Journal
CELL METABOLISM
Volume 33, Issue 2, Pages 283-+Publisher
CELL PRESS
DOI: 10.1016/j.cmet.2020.12.006
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Funding
- Fondation des Gueules Cassees
- Association Neurofibromatoses et Recklinghausen
- Fondation de l'Avenir [AP-RM-19-001]
- Association Francaise contre les Myopathies (A.F.M.) via TRANSLAMUSCLE [19507]
- 7th Framework Program of the European Commission (project REBORNE) [241879]
- Czech Science Foundation [20-18513S, 18-10832N, 20-05942S]
- Czech Health Foundation [NU20-03-00309, 17-30138A]
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Platelets enhance the therapeutic potential of MSCs by transferring mitochondria and promoting pro-angiogenic activity. Activation of the de novo fatty acid synthesis pathway is required for increased secretion of pro-angiogenic factors by platelet-preconditioned MSCs. Testing platelet mitochondria quality before clinical use is crucial for optimizing their effects.
Platelets are known to enhance the wound-healing activity of mesenchymal stem cells (MSCs). However, the mechanism by which platelets improve the therapeutic potential of MSCs has not been elucidated. Here, we provide evidence that, upon their activation, platelets transfer respiratory-competent mitochondria to MSCs primarily via dynamin-dependent clathrin-mediated endocytosis. We found that this process enhances the therapeutic efficacy of MSCs following their engraftment in several mouse models of tissue injury, including full-thickness cutaneous wound and dystrophic skeletal muscle. By combining in vitro and in vivo experiments, we demonstrate that platelet-derived mitochondria promote the pro-angiogenic activity of MSCs via their metabolic remodeling. Notably, we show that activation of the de novo fatty acid synthesis pathway is required for increased secretion of pro-angiogenic factors by platelet-preconditioned MSCs. These results reveal a new mechanism by which platelets potentiate MSC properties and underline the importance of testing platelet mitochondria quality prior to their clinical use.
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